This invention relates to new hydroxyaminohydrocarbonphosphonic acid derivatives which have antimicrobial activities against various pathogenic microorganisms, to processes for production thereof and to pharmaceutical composition comprising the same.
Firstly, it is to be noted that this invention is originated from and based upon the first and new discovery of a new antibiotic of the following formula, by isolating it from a cultured broth obtained by fermentation of a strain of the genus Streptomyces. ##STR2##
[3-(N-acetyl-N-hydroxyamino)propylphosphonic acid]
(hereinafter referred to the antibiotic FR-900098)
That is, the researchers (i.e. the inventors of U.S. application Ser. No. 819,551 filed on the same date as the filing date of this application) of the Fermentation section of the Research Laboratory of Fujisawa Pharmaceutical Co., Ltd., Japan, to which the inventors of this invention belonged, firstly and newly isolated the new antibiotic FR-900098 in pure form from a cultured broth obtained by fermentation of a strain of Streptomyces rubellomurinus ATCC No. 31215, identified the same by the physico-chemical properties and found out that the same has antimicrobial activities against various pathogenic microorganisms. Thereafter, the said antibiotic FR-900098 was delivered to the inventors of this invention for identification of the chemical structure thereof and, as the result of further study, the inventors of this invention succeeded in identifying the chemical structure and assigned the chemical structure as mentioned above to the antibiotic FR-900098.
Successively after identification of the chemical structure, the inventors of this invention have made an extensive studies on commercially advantage synthetic methods thereof, and succeeded in completing the synthetic methods for preparing the antibiotic FR-900098, and in addition to this success, the inventors of this invention succeeded in providing a lot of hydroxyaminohydrocarbonphosphonic acid derivatives other than the antibiotic FR-900098 as explained in the following disclosure of the specification.
Further, it is to be noted that the same researchers of the Fermentation section as indicated above newly discovered another antibiotic by isolating it from a culture broth obtained by fermentation of Streptomyces rubellomurinus subsp. indigoferus ATCC No. 31304 and identified the same by physico-chemical properties and also the chemical structure as assigned as follows. ##STR3##
[3-(N-acetyl-N-hydroxyamino)-2-hydroxypropylphosphonic acid] (hereinafter referred to the antibiotic FR-33289)
With regard to the antibiotic FR-33289 as stated above also, the inventors of this invention made study on the commercially advantageous synthetic process thereof, and succeeded in completing the synthetic methods for preparing the antibiotic FR-33289, too.
Incidentally, it is to be noted that the invention relating to the antibiotics FR-900098 and FR-33289 per se, the methods for preparing the same by fermentation and use thereof, was filed a the U.S. patent application under the Ser. No. 819,551 on the same date as the filing date of this application.